Cantharidin (exo,exo-2,3-dimethyl-7-oxobicyclo[2.2.1]heptane-2,3-dicarboxylic acid anhydride) is an active ingredient isolated from the Chinese blister beetles Mylabris phalerata or M. cichorii. Cantharidin has been reported to be active against various human cancers. Cantharidin's severe renal toxicity, however, limits its development as a chemotherapeutic agent. Moreover, although numerous physiological and biochemical studies have been carried out in an attempt to find the cause of growth inhibition and cell death provided by cantharidin, the critical molecular mechanism of action and pathways remain unclear.
Various derivatives of cantharidin have been investigated as potential anti-tumor agents. Synthetic norcantharidin derivatives are demethylated analogs of cantharidin. These derivatives have clinical potential as a result of causing similar growth inhibition activity as cantharidin, but have a strong suppression of renal and gastrointestinal toxicity. Cantharidic acid represents the first commercialized cantharidic anti-tumor agent to date. However, these compounds are limited by their toxicity towards the normal cells that prevent them from being effective anti-cancer drugs or chemotherapy in cancer treatment.
Consequently, it is desirable to synthesize new cantharimide compounds as cantharidin-mimics with anti-tumor effect. It is also desirable that the compounds have enhanced cytotoxicity to cancer cells, while simultaneously having reduced toxicity for normal cells. Such compounds could be useful in anti-cancer drugs or chemotherapy in cancer treatment.